P-element vectors are modified transposable elements widely used to make transgenic Drosophila. In general, insertion of P-element vectors is nonrandom, but exhibits a very broad specificity of target sites. During experiments to identify cis-acting regulatory elements of the Drosophila segmentation gene engrailed (en), we noticed that whenever a particular fragment of en DNA was included within a P-element vector, the specificity for insertion sites was strikingly altered. In particular, P elements containing a small fragment of an regulatory DNA insert at a high frequency near genes expressed in stripes. How does this selective insertion occur? We favor a model whereby a protein(s) bound to the en fragment within the P element brings it to a particular region of the genome via protein- protein or protein-DNA interactions and enhances the probability of insertion within this region. This model presumes that the genes that the "targeted" by such P elements share a common structure or location in the nucleus. We have recently cloned two of the genes which seem to be "targeted" by the en-containing transposon. Both encode zinc-finger proteins, and thus may act as transcription factors. We are comparing the sequences surrounding these genes in order to determine if common motifs are present which might be recognized by the en-transposon. Our experiments may give us insight into how transposons (or retroviruses) may acquire tissue specificity.